Article type : Case Report | تاریخ ثبت : 2015/02/20

A 44-year-old female with a remote history of autoimmune hepatitis (AIH) in remission presented with fatigue and scleral icterus, and developed fulminant liver failure within 24 hours of admission. The initiation of therapy was delayed due to the incidental finding of cholelithiasis and suspected cholecystitis. The patient was initiated on empiric antibiotics, but deteriorated rapidly. The clinical picture and history was consistent with acute severe AIH, but a low serum ceruloplasmin level and laboratory features of hemolytic anemia pointed towards fulminant Wilson’s disease. She was initiated on pulse-dose steroids, but ultimately expired from acute severe liver dysfunction and multi-organ failure. The case highlights the clinical features of AIH in the acute setting, and seeks to discuss the role of serum ceruloplasmin levels in patients with liver disease.

INTRODUCTION

Autoimmune hepatitis (AIH) is thought of as a cause of chronic liver disease accounting for approximately 20% of cases of chronic hepatitis, with an estimated annual incidence among whites of Northern Europe-an descent of 1.9 cases per 100,000.1,2 Acute severe presentations are uncommon and remain the greatest challenge with the least evidence basis to guide diag-nosis and management.1

CASE REPORT

A 44-year-old female presented to the emergency department with a 5 day history of diffuse abdom-inal pain, fatigue and scleral icterus. She reported a remote history of AIH diagnosed at the age of 18 years, for which she was treated with steroids for several years and reportedly went into remission and had been stable ever since. Past medical and surgical history was otherwise unremarkable. She denied the use of herbal or alternative remedies. She also denied smoking, alcohol or illicit drug use. Family history was unremarkable. Physical examination revealed normal vital signs, a normal respiratory, cardiovascular and neurologic ex-aminations, and the abdomen was mildly tender in the right upper quadrant. Initial laboratory tests showed a leukocyte count of 22 k/uL, hemoglobin of 8.4 g/dL, platelet count of 290 k/uL, BUN of 38 mg/dL, creat-inine of 1.8 mg/dL. Liver studies showed an AST of 110 U/L, ALT of 29 U/L, alkaline phosphatase of 100 U/L, total bilirubin of 14.2 mg/dL, albumin of 1.9, and INR of 3.3. An abdominal ultrasound of the liver and biliary tree revealed normal echogenicity of the liver and a few echogenic structures within the gall-bladder with gallbladder wall thickening. She was given vitamin K in an attempt to reverse the coag-ulopathy. Empiric antibiotics were initiated for sus-pected cholecystitis after consultation with the sur-gical team. A work-up for potential causes of acute liver failure was initiated. This included serum acet-aminophen and alcohol levels, a viral hepatitis panel, anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti-liver/kidney microsome type 1 (LKM-1) antibody, and ceruloplasmin. Over the following 24 hours, the patient’s kidney function deteriorated further despite adequate intra-venous fluid hydration. Her creatinine increased to 2.7 mg/dL and potassium to 7 mmol/L, and she was becoming acidotic. The AST was 300 U/L, total bil-irubin was 20 mg/dL, and INR was 4 after vitamin K administration. The hemoglobin dropped with a repeat of 7.6 g/dL. A hemolytic work-up revealed a haptoglobin of

DISCUSSION

The initial presentation of fulminant liver failure can be unclear and an exact etiology can be difficult to determine. However, in patients with a reported history of AIH, the possibility of a spontaneous exacerbation of the pre-existent chronic disease must be consid-ered. The diagnostic criteria developed by the International Autoimmune Hepatitis Group can help aid in the diagnosis of acute presentations.3 They involve examining multiple facets of the presentation, includ-ing serum biochemistry, immunoglobulins, antibodies, viral markers, history of ingestion of hepatotoxic drugs, and histologic findings. The main findings that form the scoring system in-clude; abnormalities in aminotransferases with a nor-mal alkaline phosphatase and normal ceruloplasmin, serum IgG concentrations greater than 1.5 times the upper limit of normal, seropositivity for ANA, SMA, or anti LKM-1 antibodies with titers > 1:80, negative viral markers for hepatitis A, B, and C viruses, no history of ingestion of hepatotoxic drugs of heavy al-cohol consumption, and characteristic histologic fea-tures. The scoring system defines probable AIH with a score of 10-15, and definite AIH with a score of more than 15.4, 5 The present patient had a score of 18 making the diagnosis of AIH “definite”. The reported history of AIH classified the current presentation as a relapse of chronic disease. Furthermore, Kessler et al described characteristic biochemical features seen more commonly with acute presentations. These in-cluded significantly lower albumin levels, and higher total bilirubin levels, as seen in the present patient.2 Hypoalbuminemia most likely reflects the acute phase reactant properties of this variable rather than a marker of chronic liver disease.3 The cornerstone of therapy when suspecting AIH is corticosteroids with or without azathioprine. The combination has been reported to induce clinical and laboratory improvement in 68-75% of patients with acute presentations. Corticosteroids alone can be effective, but the efficacy is unclear with reports ranging from 20-100% response in acute severe pre-sentations.4 Mortality is unavoidable when laboratory parameters fail to improve within 2 weeks of corti-costeroid therapy. Specifically, hyperbilirubinemia that fails to improve is highly predicative of the need for urgent transplantation.6 Involvement of the liver transplant team should be initiated early, and trans-plantation should not be delayed or superseded by protracted corticosteroid therapy of the institution or other nonstandard medications.4, 6 Ceruloplasmin is an alpha-2 glycoprotein synthesized in the liver, which functions as a copper-binding pro-tein. Serum ceruloplasmin is used as a screening test for Wilson’s disease, in which low levels are indica-tive of the condition and normal levels point towards an alternative diagnosis.7, 8 The present patient was puzzling in that she had biochemical findings sug-gestive of fulminant Wilson’s disease. Ultimately, the lack of neuropsychiatric disease, KF rings, sero-positivity for SMA, and normal alkaline phosphatase made the diagnosis of Wilson’s disease debatable. The distinction is important and can be difficult in the acute setting. Management for acute severe AIH would include corticosteroids and azathioprine, while fulminant Wilson’s disease would require initiation of plasmapheresis9, either of which should occur while concurrently evaluating the patient for emergency OLT. Low ceruloplasmin levels can be seen in other caus-es of acute and chronic liver diseases. Cauza et al screened patients with liver disease by measuring se-rum ceruloplasmin levels and found that out of 17 pa-tients with levels

CONCLUSION

Clinical decision making in the setting of fulminant liver failure largely involves supportive care, initi-ation of targeted therapy, and early involvement of the liver transplant team. Acute severe AIH should be suspected in patients with hyperbilirubinemia and hypoalbuminemia, especially with a reported histo-ry of AIH. When suspecting acute severe AIH, phy-sicians should have a low threshold for initiation of corticosteroid therapy with or without azathioprine to prevent morbidity and mortality. Finally, a low ceru-loplasmin level is seen in multiple conditions causing acute or chronic liver disease and is not specific to Wilson’s disease, but should prompt further work-up to measure serum and urine copper levels.